Conjugate vaccines of polysaccharides (PS; including lipopolysaccharides or LPS) utilize a carrier protein as a vehicle to convert the T-independent immunogen PS to a T- dependent protein-PS conjugate, and thus afford the protection to an otherwise PS-non-responding population such as infants and the aged. In this research, we investigate the issues related to the chemistries of conjugate vaccine synthesis and their impacts to the vaccine immunogenicity and effectiveness. This includes the studies of: 1) the structures of PS and LPS, carrier protein and peptides, spacer molecules and the conjugates, 2) conditions of chemical reactions for conjugate formation, and 3) characterization of the conjugates in the aspects of physical and chemical properties and immunology. We have synthesized PS-tetanus toxoid (TT) conjugates for pneumococcal types 4, 6B, 9V, 14, 18C, 19F and 23F. The immunogenicity of these singular and combined 7-valent conjugates were investigated in mice in parallel with the corresponding PS-CRM197 conjugates vaccine candidates of Wyeth-Lederle Vaccines and Pediatrics. It was found that the PS-CRM197 conjugates were more immunogenic than the PS-TT conjugates. The conjugates in singular form were more effective as an immunogen than in the combined 7-valent form except for T4 PS- CRM197 and T23F PS-TT. Opsonophagocytosis activity of the elicited antisera will be determined and correlated with the antibody content. In another line of research, we have conjugated LPS from mutants of group B menigococci and B. pertussis to TT. These conjugates exhibit T-dependent immunogenicity against homologous LPS, and have a remarkable reduction of LAL activity. The bactericidal activities of the antibodies induced by these conjugates are currently being measured in vitro and in vivo